tbuckley/cabot-search huggingface dataset:
Joint learning framework of cross-modal synthesis and diagnosis for Alzheimer’s disease by mining underlying shared modality information
Authors: Chenhui Wang, Sirong Piao, Zhizhong Huang, Qi Gao, Junping Zhang, Yuxin Li, Hongming Shan
Journal: Medical Image Analysis (2023)

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders presenting irreversible progression of cognitive impairment. How to identify AD as early as possible is critical for intervention with potential preventive measures. Among various neuroimaging modalities used to diagnose AD, functional positron emission tomography (PET) has higher sensitivity than structural magnetic resonance imaging (MRI), but it is also costlier and often not available in many hospitals. How to leverage massive unpaired unlabeled PET to improve the diagnosis performance of AD from MRI becomes rather important. To address this challenge, this paper proposes a novel joint learning framework of unsupervised cross-modal synthesis and AD diagnosis by mining underlying shared modality information, improving the AD diagnosis from MRI while synthesizing more discriminative PET images. We mine underlying shared modality information in two aspects: diversifying modality information through the cross-modal synthesis network and locating critical diagnosis-related patterns through the AD diagnosis network. First, to diversify the modality information, we propose a novel unsupervised cross-modal synthesis network, which implements the inter-conversion between 3D PET and MRI in a single model modulated by the AdaIN module. Second, to locate shared critical diagnosis-related patterns, we propose an interpretable diagnosis network based on fully 2D convolutions, which takes either 3D synthesized PET or original MRI as input. Extensive experimental results on the ADNI dataset show that our framework can synthesize more realistic images, outperform the state-of-the-art AD diagnosis methods, and have better generalization on external AIBL and NACC datasets.
Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality
Authors: Steven D Nathan, Shilpa Johri, Joanna M Joly, Christopher S King, Amresh Raina, Colleen A McEvoy, Dasom Lee, Eric Shen, Peter Smith, Chunqin Deng, Aaron B Waxman
Journal: Thorax (2023)

Objective A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). Methods Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs. Results In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively. Conclusion Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD.
Formylpeptide receptor 1 contributes to epidermal barrier dysfunction-induced skin inflammation through NOD-like receptor C4-dependent keratinocyte activation
Authors: Shuai Shao, Zhongbin Sun, Mengyang Chu, Jiaoling Chen, Tianyu Cao, William R Swindell, Yaxing Bai, Qingyang Li, Jingyi Ma, Zhenlai Zhu, Andrew Schuler, Yolanda Helfrich, Allison C Billi, Zhiguo Li, Junfeng Hao, Chunying Xiao, Erle Dang, Johann E Gudjonsson, Gang Wang
Journal: British Journal of Dermatology (2023)

Abstract Background Skin barrier dysfunction may both initiate and aggravate skin inflammation. However, the mechanisms involved in the inflammation process remain largely unknown. Objectives We sought to determine how skin barrier dysfunction enhances skin inflammation and molecular mechanisms. Methods Skin barrier defect mice were established by tape stripping or topical use of acetone on wildtype mice, or filaggrin deficiency. RNA-Seq was employed to analyse the differentially expressed genes in mice with skin barrier defects. Primary human keratinocytes were transfected with formylpeptide receptor (FPR)1 or protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) small interfering RNA to examine the effects of these gene targets. The expressions of inflammasome NOD-like receptor (NLR)C4, epidermal barrier genes and inflammatory mediators were evaluated. Results Mechanical (tape stripping), chemical (acetone) or genetic (filaggrin deficiency) barrier disruption in mice amplified the expression of proinflammatory genes, with transcriptomic profiling revealing overexpression of formylpeptide receptor (Fpr1) in the epidermis. Treatment with the FPR1 agonist fMLP in keratinocytes upregulated the expression of the NLRC4 inflammasome and increased interleukin-1β secretion through modulation of ER stress via the PERK-eIF2α-C/EBP homologous protein pathway. The activation of the FPR1-NLRC4 axis was also observed in skin specimens from old healthy individuals with skin barrier defect or elderly mice. Conversely, topical administration with a FPR1 antagonist, or Nlrc4 silencing, led to the normalization of barrier dysfunction and alleviation of inflammatory skin responses in vivo. Conclusions In summary, our findings show that the FPR1-NLRC4 inflammasome axis is activated upon skin barrier disruption and may explain exaggerated inflammatory responses that are observed in disease states characterized by epidermal dysfunction. Pharmacological inhibition of FPR1 or NLRC4 represents a potential therapeutic target.
OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes
Authors: Emmaline Prinz, Leoni Schlupp, Gabby Dyson, Montana Barrett, Aleksander Szymczak, Cassandra Velasco, Vladislav Izda, Christopher M Dunn, Matlock A Jeffries
Journal: Annals of the Rheumatic Diseases (2023)

The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised microbiome differences between MRL and wild-type mice, evaluated microbiome transplantation and OA and investigated microbiome-associated immunophenotypes.
Determining the core content of a digital survivorship care plan for melanoma survivors: a multistakeholder Delphi consensus study
Authors: Nadia C W Kamminga, Marlies Wakkee, Inez Swart, Tamar E C Nijsten, Marjolein Lugtenberg
Journal: British Journal of Dermatology (2023)

Increasing melanoma incidence and improved survival emphasize the importance of survivorship care plans (SCPs). We conducted a multistakeholder Delphi study to achieve consensus on core melanoma SCP content. Of the 44 potential elements, 24 (55%) reached consensus for inclusion. Notably, melanoma survivors and healthcare providers differed in their preferences, with survivors prioritizing coordination improvements and healthcare providers emphasizing psychosocial care. Exploring and overcoming these differences in opinions and including the consented elements as a basis in the design of the SCP can facilitate its implementation in practice and lead to survivorship care tailored to stakeholders’ needs.
Apoptotic MSCs, COX2/PGE2 and clinical efficacy in Crohn fistula
Authors: Karen English
Journal: Molecular Therapy (2023)

The clinical application of mesenchymal stromal cells (MSCs) has been approved for use in pediatric graft-versus-host disease (GvHD) and perianal fistulizing Crohn disease. MSCs have also been investigated in an array of other inflammatory disease indications. Despite promising results in patients who respond to MSC administration, a significant proportion of patients do not respond, and this has significantly dampened enthusiasm for MSC-based cell therapy. A better understanding of the mechanism of action (MOA) involved in the therapeutic effects of MSCs may help to stratify patients who will respond to MSC administration. In this issue of Molecular Therapy, Cheung et al. publish their findings on the role of caspase-mediated apoptosis of MSCs, leading to the release of immunosuppressive factors, including prostaglandin E2 (PGE2), which correlated with clinical responsiveness in Crohn's disease patients.1 The authors build upon on their previous study that identified a correlation between the induction of apoptosis mediated by peripheral blood mononuclear cells (PBMCs) from patients with GvHD who responded to MSC administration.2 In the present article, Cheung et al. demonstrate once again a correlation between apoptosis induction in MSCs and a role for cyclooxygenase 2 (COX2)/PGE2 in mediating immunosuppressive effects in patients with Crohn's disease who responded to MSC therapy.1 The significance of this study is that it identifies potential assays that could be used to stratify patients based on the capacity of patient PBMCs to induce MSC apoptosis and/or the use of PGE2 levels produced from PBMC-induced apoptotic MSCs.
Hidden variables in stress neurobiology research
Authors: Ashley L. Holloway, Talia N. Lerner
Journal: Trends in Neurosciences (2023)

Among the central goals of stress neurobiology research is to understand the mechanisms by which stressors change neural circuit function to precipitate or exacerbate psychiatric symptoms. Yet despite decades of effort, psychiatric medications that target the biological substrates of the stress response are largely lacking. We propose that the clinical advancement of stress response-based therapeutics for psychiatric disorders may be hindered by 'hidden variables' in stress research, including considerations of behavioral study design (stressors and outcome measures), individual variability, sex differences, and the interaction of the body's stress hormone system with endogenous circadian and ultradian rhythms. We highlight key issues and suggest ways forward in stress neurobiology research that may improve the ability to assess stress mechanisms and translate preclinical findings.
Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis
Authors: Dorota Kujawa, Lukasz Laczmanski, Slawomir Budrewicz, Anna Pokryszko-Dragan, Maria Podbielska
Journal: Gut Microbes (2023)

Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.
Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing
Authors: Tongyu Huo, Xinyi Zhao, Zengrui Cheng, Jialiang Wei, Minghui Zhu, Xiaodong Dou, Ning Jiao
Journal: Acta Pharmaceutica Sinica B (2023)

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead compounds optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new drug is to start with an old drug"
What stakeholders with neurodegenerative conditions value about speed and accuracy in development of BCI systems for communication
Authors: Melanie Fried-Oken, Michelle Kinsella, Ian Stevens, Eran Klein
Journal: Brain-Computer Interfaces (2023)

This research examined values of individuals with neurodegenerative conditions about features of speed and accuracy as they consider potential use of augmentative and alternative communication brain-computer interface systems (AAC-BCI). Sixty-six individuals with neurodegenerative disease responded to prompts about six hypothetical ethical vignettes. Data were analyzed with qualitative content analysis. The following themes emerged. (1) Disease progression may contribute to the trade-off between speed and accuracy with AAC-BCI systems. (2) Individual experiences with technology use inform their views about the speed-accuracy trade-off. (3) There is a range of views about how slow or inaccurate communication may impact relationships, the integrity of a message, and quality of life. (4) Design solutions are proposed to address trade-offs in AAC-BCI systems. With the rapid development of AAC-BCI systems, user-centered design must integrate values of potential end-users illustrating that context, partner, message, and environment impact the prioritization of speed or accuracy in any communication exchange.
Long-term mortality in treated-to-target RA and UA: results of the BeSt and IMPROVED cohort
Authors: Sascha Louise Heckert, Johanna Maria Maassen, S le Cessie, Y P M Goekoop-Ruiterman, Melek Güler-Yüksel, Willem Lems, Tom WJ Huizinga, Sytske Anne Bergstra, Cornelia F Allaart
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To study long-term (up to 20-year) mortality of two treat-to-target trial cohorts in undifferentiated arthritis (UA) and early rheumatoid arthritis (RA). Methods The BeSt (BehandelStrategieën) study (n=508, early RA) was performed between 2000 and 2012. For 10 years, patients were treated-to-target disease activity score (DAS)≤2.4. The Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED) study (n=610, early RA/UA) was performed between 2007 and 2015. For 5 years, patients were treated-to-target DAS&lt;1.6. Vital status of BeSt/IMPROVED participants was assessed up to and including 31 December 2021. Standardised mortality ratios (SMRs) were calculated. Stratified analyses for anticitrullinated protein antibody (ACPA) and smoking status were performed. Death causes and the potential effect of disease activity during the trial period on late mortality were assessed. Results Excess mortality was found in both BeSt (SMR 1.32, 95% CI 1.14 to 1.53) and IMPROVED (SMR 1.33, 95% CI 1.10 to 1.63) and became manifest after 10 years. Excess mortality was statistically significant in ACPA+ patients who smoked (BeSt: SMR 2.80, 95% CI 2.16 to 3.64; IMPROVED: 2.14, 95% CI 1.33 to 3.45). Mean survival time was 10 (95% CI 5 to 16) months shorter than expected in BeSt and 13 (95% CI 11 to 16) months in IMPROVED. The HR for mortality was 1.34 (95% CI 0.96 to 1.86; BeSt)/1.13 (95% CI 0.67 to 1.91; IMPROVED) per 1 point increase in mean DAS during the trial. The main cause of death was malignancy. Conclusions After long-term treatment-to-target, excess mortality occurred in patients with RA after&gt;10 years since treatment start, with smoking as an important risk factor.
Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial
Authors: Duvuru Geetha, Anisha Dua, Huibin Yue, Jason Springer, Carlo Salvarani, David Jayne, Peter Merkel
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. Methods Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. Results Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. Conclusions These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. Trial registration number NCT02994927 .
The phase 2 LYSA study of prednisone, vinblastine, doxorubicin, and bendamustine for untreated Hodgkin lymphoma in older patients
Authors: Hervé Ghesquières, Daphné Krzisch, Emmanuelle Nicolas-Virelizier, Salim Kanoun, Anne Claire Gac, Stéphanie Guidez, Mohamed Touati, Kamel Laribi, Franck Morschhauser, Christophe Bonnet, Agathe Waultier-Rascalou, Frédérique Orsini-Piocelle, Marc André, Marguerite Fournier, Fabienne Morand, Alina Berriolo-Riedinger, Barbara Burroni, Diane Damotte, Alexandra Traverse-Glehen, Philippe Quittet, Olivier Casasnovas
Journal: Blood (2023)
Expression quantitative trait loci analysis in rheumatoid arthritis identifies tissue specific variants associated with severity and outcome
Authors: Katriona Goldmann, Athina Spiliopoulou, Andrii Iakovliev, Darren Plant, Nisha Nair, Cankut Cubuk, Paul McKeigue, Michael R Barnes, Anne Barton, Costantino Pitzalis, Myles J Lewis
Journal: Annals of the Rheumatic Diseases (2023)

Objective Genome-wide association studies have successfully identified more than 100 loci associated with susceptibility to rheumatoid arthritis (RA). However, our understanding of the functional effects of genetic variants in causing RA and their effects on disease severity and response to treatment remains limited. Methods In this study, we conducted expression quantitative trait locus (eQTL) analysis to dissect the link between genetic variants and gene expression comparing the disease tissue against blood using RNA-Sequencing of synovial biopsies (n=85) and blood samples (n=51) from treatment-naïve patients with RA from the Pathobiology of Early Arthritis Cohort. Results This identified 898 eQTL genes in synovium and genes loci in blood, with 232 genes in common to both synovium and blood, although notably many eQTL were tissue specific. Examining the HLA region, we uncovered a specific eQTL at HLA-DPB2 with the critical triad of single-nucleotide polymorphisms (SNPs) rs3128921 driving synovial HLA-DPB2 expression, and both rs3128921 and HLA-DPB2 gene expression correlating with clinical severity and increasing probability of the lympho-myeloid pathotype. Conclusions This analysis highlights the need to explore functional consequences of genetic associations in disease tissue. HLA-DPB2 SNP rs3128921 could potentially be used to stratify patients to more aggressive treatment immediately at diagnosis.
Effects of non-invasive ventilation on sleep in chronic hypercapnic respiratory failure
Authors: Neeraj M Shah, Joerg Steier, Nicholas Hart, Georgios Kaltsakas
Journal: Thorax (2023)

Chronic respiratory disease can exacerbate the normal physiological changes in ventilation observed in healthy individuals during sleep, leading to sleep-disordered breathing, nocturnal hypoventilation, sleep disruption and chronic respiratory failure. Therefore, patients with obesity, slowly and rapidly progressive neuromuscular disease and chronic obstructive airways disease report poor sleep quality. Non-invasive ventilation (NIV) is a complex intervention used to treat sleep-disordered breathing and nocturnal hypoventilation with overnight physiological studies demonstrating improvement in sleep-disordered breathing and nocturnal hypoventilation, and clinical trials demonstrating improved outcomes for patients. However, the impact on subjective and objective sleep quality is dependent on the tools used to measure sleep quality and the patient population. As home NIV becomes more commonly used, there is a need to conduct studies focused on sleep quality, and the relationship between sleep quality and health-related quality of life, in all patient groups, in order to allow the clinician to provide clear patient-centred information.
Evaluating bimekizumab safety
Authors: Katie Lovell, Steven R Feldman
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Evaluating bimekizumab safety Get access Katie Lovell, Katie Lovell Conceptualization, Writing - original draft, Writing - review & editing Departments of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA Correspondence: Katie Lovell. Email: kennedyka20@students.ecu.edu https://orcid.org/0009-0005-0098-8455 Search for other works by this author on: Oxford Academic Google Scholar Steven R Feldman Steven R Feldman Conceptualization, Supervision, Writing - review & editing Departments of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USADepartments of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USADepartments of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, USA Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad451, https://doi.org/10.1093/bjd/ljad451 Published: 18 November 2023 Article history Received: 05 November 2023 Accepted: 10 November 2023 Published: 18 November 2023 Corrected and typeset: 20 December 2023